Organocatalysis is a subdivision of catalysis which relies on the use of wholly organic molecules as catalysts. These catalysts are very useful and have already made significant contributions in the production and discovery of new pharmaceuticals, agrochemicals and other high added value compounds (Alemán and Cabrera, 2013, MacMillan, 2008). The discovery of the Hajos-Parrish-Eder-Sauer-Wiechert reaction was the starting point (Eder et al. 1971, Hajos et al. 1974). But only relatively recently has there been a renaissance of this field, when Barbas III, Lerner, List and MacMillan applied very successfully simple small molecule organocatalysts (for example, L-proline and derivatives and imidazolidinones) in intermolecular aldol and Michael addition reactions, etc.
In general the catalysts are optically pure and the reactions highly enantioselective. Organocatalysts based on the Cinchona skeleton are known, and very good results have been reported for a diversity of reactions, like, conjugate additions (Hiemstra e Wynberg, 1981), Michael additions and Mannich reactions (Ye et al., 2005, Tillman et al. 2006, McCooey and Connon 2005), and phase-transfer catalysis (Chinchilla et al. 2000) amongst other reactions. Picolinamide based organocatalysts have also been reported and have been exploited with success in the hydrosilylation reaction of N-substituted imines (Guizzetti et al. 2009, Zheng et al. 2007) and in asymmetric Biginelli reactions (Xu et al. 2012).
Many chiral amines have been shown to be biologically active. 45% of molecules that chemists are developing into drugs contain a chiral amine unit (Ritter, 2013), well known examples include: rivastagimine, rasagline, sertraline, indatraline (Hyttel and Larsen, 1985) cetirizine and cromakilm etc.
Picolinamides, which are amides derived from picolinic acid have been incorporated into a number of carbon skeletons and used very successfully as organocatalysts in a number of reactions. For example in the asymmetric Biginelli reaction (Xu et al. 2012) in which the bifunctional organocatalyst of formula I:
which contains a primary amine linked to a picolinamide unit, is used in the reaction:

Another example is in the area of ketimine hydrosilylation using trichlorosilane as the reducing agent where the N-picolinoylaminoalcohol of formula II:
gave excellent results (Zheng et al. 2007) in the reaction with a catalyst loading of 10 mol %.

There are other examples in the literature (Guizzetti et al. 2009, Bonsignore et al. 2013, Onomura et al. 2006 and Jones and Warner, 2012). However, there aren't any reports on the synthesis and use of N-alkylated cinchona picolinamides.
The catalytic asymmetric hydrosilylation reaction of ketimines is extremely useful from an industrially perspective, as it affords chiral amines (Nugent and El-Shazly, 2010, Ghose et al. 1999), amino acids and other high valued products. Traditionally, the hydrogenation of ketimines is conducted using metal based catalysts (Nishiyama and Itoh, 2000). For decades, catalysis by way of metals has been the dominant form of catalysis, the principle advantages are that a variety of transition metals and ligands can be used and the catalysts tuned on this basis, and the loadings are generally low. Despite these advantages, the downside is that these catalysts are expensive, generally unstable to oxygen/water and to recycling, some are toxic and they generally end-up in the final product in small quantities (Busacca et al. 2011). This is less of a problem for most organocatalysts.
Quite recently, a number of groups have used organocatalysts in the hydrosilylation of ketimines, and have obtained good yields and enantioselectivities (Jones and Warner, 2012, Malkov et al. 2006, Bonsignore et al. 2013, Wang et al. 2006 and Wu et al. 2008). In fact, this methodology was nicely shown to be a viable approach to the commercial herbicide; (S)-Metolachlor (Guizzetti et al., 2009).
There have been several reports to date on the use of supported organocatalysts, (Cozzi, 2006, Kristensen and Tore, 2010), including the use of magnetic nanoparticles (Gleeson et al. 2011). However there have been no reports on the immobilization of picolinamide organocatalysts or derivatives.
The present disclosure describes a novel type of picolinamide-cinchona organocatalyst that allows for the successful transformation of ketimines to chiral amines with very high enantioselectivities and with the highest TOFs reported for any particular organocatalyst to date. These organocatalysts have also been immobilized to a variety of solid supports, including magneto-nanoparticles.